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Experimental Eye Research Oct 2016The small leucine rich repeat proteoglycans are major components of the cornea. Lumican, keratocan, decorin, biglycan and osteoglycin are present throughout the adult... (Review)
Review
The small leucine rich repeat proteoglycans are major components of the cornea. Lumican, keratocan, decorin, biglycan and osteoglycin are present throughout the adult corneal stroma, and fibromodulin in the peripheral limbal area. In the cornea literature these proteoglycan have been reviewed as structural, collagen fibril-regulating proteins of the cornea. However, these proteoglycans are members of the leucine-rich-repeat superfamily, and share structural similarities with pathogen recognition toll-like receptors. Emerging studies are showing that these have a range of interactions with cell surface receptors, chemokines, growth factors and pathogen associated molecular patterns and are able to regulate host immune response, inflammation and wound healing. This review discusses what is known about their innate immune-related role directly in the cornea, and studies outside the field that find interesting links with innate immune and wound healing responses that are likely to be relevant to the ocular surface. In addition, the review discusses phenotypes of mice with targeted deletion of proteoglycan genes and genetic variants associated with human pathologies.
Topics: Animals; Cornea; Corneal Injuries; Humans; Keratitis; Small Leucine-Rich Proteoglycans; Wound Healing
PubMed: 27569372
DOI: 10.1016/j.exer.2016.08.015 -
Atherosclerosis Mar 2014Subendothelial LDL retention by intimal matrix proteoglycans is an initial step in atherosclerosis and calcific aortic valve disease. Herein, we identify decorin and...
OBJECTIVE
Subendothelial LDL retention by intimal matrix proteoglycans is an initial step in atherosclerosis and calcific aortic valve disease. Herein, we identify decorin and biglycan as the proteoglycans that preferentially retain LDL in intimal matrix at disease-prone sites in normal valve and vessel wall.
METHODS
The porcine aortic valve and renal artery ostial diverter, initiation sites of calcific valve disease and renal atherosclerosis, respectively, from normal non-diseased animals were used as models in these studies.
RESULTS
Fluorescent human LDL was selectively retained on the lesion-prone collagen/proteoglycan-enriched aortic surface of the valve, where the elastic lamina is depleted, as previously observed in lesion-prone sites in the renal ostium. iTRAQ mass spectrometry of valve and diverter protein extracts identified decorin and biglycan as the major subendothelial intimal matrix proteoglycans electrostatically retained on human LDL affinity columns. Decorin levels correlated with LDL binding in lesion-prone sites in both tissues. Collagen binding to LDL was shown to be proteoglycan-mediated. All known basement membrane proteoglycans bound LDL suggesting they may modulate LDL uptake into the subendothelial matrix. The association of purified decorin with human LDL in an in vitro microassay was blocked by serum albumin and heparin suggesting anti-atherogenic roles for these proteins in vivo.
CONCLUSIONS
LDL electrostatic interactions with decorin and biglycan in the valve leaflets and vascular wall is a major source of LDL retention. The complementary electrostatic sites on LDL or these proteoglycans may provide a novel therapeutic target for preventing one of the earliest events in these cardiovascular diseases.
Topics: Animals; Aortic Valve; Atherosclerosis; Biglycan; Calcinosis; Cardiomyopathies; Decorin; Humans; Lipoproteins, LDL; Proteomics; Static Electricity; Swine; Tunica Intima
PubMed: 24529131
DOI: 10.1016/j.atherosclerosis.2013.12.038 -
European Cells & Materials Oct 2003This paper reviews our current state of knowledge of the roles the small leucine-rich proteoglycans (SLRPs) play in the formation of connective tissue and mineralised... (Comparative Study)
Comparative Study Review
This paper reviews our current state of knowledge of the roles the small leucine-rich proteoglycans (SLRPs) play in the formation of connective tissue and mineralised tissue matrices. Both, the SLRPs biglycan and decorin are highly expressed in extracellular bone matrix and there is now substantial evidence to support an increasing role for biglycan and decorin in influencing bone cell differentiation and proliferative activity. In addition decorin and biglycan have been implicated in regulating mineral deposition and crystal morphology, whilst decorin has also roles in organic matrix assembly. In order to further assess the role of these SLRPs during bone formation we have initiated studies investigating primary bone cell culture models from rats (bone marrow stromal cells, and bone cells from alveolar bone explants), and identified periods relating to cell proliferation, organic matrix deposition, remodeling of the osteoid, and mineral deposition. Analysis of mRNA levels and the nature of the proteoglycan demonstrated that dermatan sulphate substituted biglycan was expressed during phases relating to cell proliferation, ceased at early matrix deposition, and then biglycan was re-expressed at the onset of mineralisation, but was conjugated to chondroitin sulphate. Decorin was expressed later than biglycan, was associated with early matrix deposition, but then continued to the mineralisation stages. Again, dermatan sulphate-decorin prevailed earlier within osteoid matrix, whilst chondroitin sulphate-decorin predominated later within the mineralizing matrix. The nature of the GAG chain conjugated to SLRP and the timing of its expression would seem to dictate the functions biglycan and decorin play in bone formation.
Topics: Animals; Biglycan; Decorin; Extracellular Matrix Proteins; Humans; Leucine; Osteogenesis; Proteoglycans
PubMed: 14562268
DOI: 10.22203/ecm.v006a02 -
Data in Brief Apr 2023This dataset is composed of photomicrographs of the immunohistochemical expression of Biglycan (BGN) in breast tissue, with and without cancer, using only the staining...
This dataset is composed of photomicrographs of the immunohistochemical expression of Biglycan (BGN) in breast tissue, with and without cancer, using only the staining of 3-3' diaminobenzidine (DAB), after processing images with color deconvolution plugin, from Image J. The immunohistochemical DAB expression of BGN was obtained using the monoclonal antibody (M01) (clone 4E1-1G7 - Abnova Corporation, mouse anti-human). Photomicrographs were obtained, under standard conditions, using an optical microscope, with UPlanFI 100x objective (resolution: 2.75 mm), yielding an image size of 4800 × 3600 pixels. After color deconvolution, the dataset with 336 images was divided into 2 two categories: (I) with cancer and (II) without cancer. This dataset allows the training and validation of machine learning models to diagnose, recognize and classify the presence of breast cancer, using the intensity of the colors of the BGN.
PubMed: 36879615
DOI: 10.1016/j.dib.2023.108978 -
IScience Sep 2023Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal cancer (CRC), which is negatively...
Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal cancer (CRC), which is negatively associated with survival rates in patients with CRC. However, how the proteoglycan promotes the progress of CRC through interacting with bacteria and regulating the immune response of enteric neurons remains largely unknown. In the present study, we found that biglycan deficiency changed tumor distribution in a colitis-associated colon cancer model. Furthermore, we revealed that BGN deficiency inhibits tumor growth in an allograft tumor model and the migration of cancer cell by upregulating interleukin-10 expression in enteric neurons. Significantly, we demonstrated that biglycan deficiency enriched the abundance of through competing with it for chondroitin sulfate to inhibit CRC progress. Our work provided new insights into the interaction between host proteoglycan and gut microbiota as well as the role of enteric neurons in the tumor microenvironment.
PubMed: 37664615
DOI: 10.1016/j.isci.2023.107515 -
Clinical and Translational Medicine Feb 2023Cancer-associated fibroblasts (CAFs) are correlated with the immunotherapy response. However, the culprits that link CAFs to immunotherapy resistance are still rarely...
Dissecting the role of cancer-associated fibroblast-derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single-cell transcriptomic study.
INTRODUCTION
Cancer-associated fibroblasts (CAFs) are correlated with the immunotherapy response. However, the culprits that link CAFs to immunotherapy resistance are still rarely investigated in real-world studies.
OBJECTIVES
This study aims to systematically assess the landscape of fibroblasts in cancer patients by combining single-cell and bulk profiling data from pan-cancer cohorts. We further sought to decipher the expression, survival predictive value and association with immunotherapy response of biglycan (BGN), a proteoglycan in the extracellular matrix, in multiple cohorts.
METHODS
Pan-cancer tumor bulks and 27 single-cell RNA sequencing cohorts were enrolled to investigate the correlations and crosstalk between CAFs and tumor or immune cells. Specific secreting factors of CAFs were then identified by expression profiling at tissue microdissection, isolated primary fibroblasts and single-cell level. The role of BGN was further dissected in additional three bulk and five single-cell profiling datasets from immunotherapy cohorts and validated in real-world patients who have received PD-1 blockade using immunohistochemistry and immunofluorescence.
RESULTS
CAFs were closely correlated with immune components. Frequent crosstalk between CAFs and other cells was revealed by the CellChat analysis. Single-cell regulatory network inference and clustering identified common and distinct regulators for CAFs across cancers. The BGN was determined to be a specific secreting factor of CAFs. The BGN served as an unfavourable indicator for overall survival and immunotherapy response. In the real-world immunotherapy cohort, patients with high BGN levels presented a higher proportion of poor response compared with those with low BGN (46.7% vs. 11.8%) and a lower level of infiltrating CD8+ T cells was also observed.
CONCLUSIONS
We highlighted the importance of CAFs in the tumor microenvironment and revealed that the BGN, which is mainly derived from CAFs, may be applicable in clinical practice and serve as a therapeutic target in immunotherapy resistance.
Topics: Humans; Transcriptome; Cancer-Associated Fibroblasts; Biglycan; Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 36772945
DOI: 10.1002/ctm2.1189 -
Cell Reports Jun 2020Obesity is characterized by adipose tissue inflammation. Because proteoglycans regulate inflammation, here we investigate their role in adipose tissue inflammation in...
Obesity is characterized by adipose tissue inflammation. Because proteoglycans regulate inflammation, here we investigate their role in adipose tissue inflammation in obesity. We find that adipose tissue versican and biglycan increase in obesity. Versican is produced mainly by adipocytes and biglycan by adipose tissue macrophages. Both proteoglycans are also present in adipose tissue from obese human subjects undergoing gastric bypass surgery. Deletion of adipocyte-specific versican or macrophage-specific biglycan in mice reduces macrophage accumulation and chemokine and cytokine expression, although only adipocyte-specific versican deletion leads to sustained improvement in glucose tolerance. Macrophage-derived biglycan activates inflammatory genes in adipocytes. Versican expression increases in cultured adipocytes exposed to excess glucose, and adipocyte-conditioned medium stimulates inflammation in resident peritoneal macrophages, in part because of a versican breakdown product, versikine. These findings provide insights into the role of adipocyte- and macrophage-derived proteoglycans in adipose tissue inflammation in obesity.
Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Biglycan; Bone Marrow; Diet, High-Fat; Female; Glucose Tolerance Test; Humans; Hypertrophy; Inflammation; Insulin Resistance; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Middle Aged; Obesity; Omentum; Organ Specificity; RNA, Messenger; Subcutaneous Fat; Versicans
PubMed: 32610121
DOI: 10.1016/j.celrep.2020.107818 -
Reproductive Sciences (Thousand Oaks,... Aug 2020Preterm birth is a leading cause of neonatal mortality in the US and globally, with preterm premature rupture of fetal membranes (PPROM) accounting for one third of...
Preterm birth is a leading cause of neonatal mortality in the US and globally, with preterm premature rupture of fetal membranes (PPROM) accounting for one third of preterm births. Currently no predictive diagnostics are available to precisely assess risk and potentially reduce the incidence of PPROM. Bigycan and decorin, the main proteoglycans present in human fetal membranes, are involved in the physiological maturation of fetal membranes as well as in the pathophysiology of preterm birth. The serum protein sex hormone-binding globulin (SHBG) has recently been identified as a predictor of spontaneous preterm birth. We hypothesize that the balance between serum decorin and biglycan on one hand and SHBG on the other hand may provide insight into the status of the fetal membranes in early pregnancy, thereby predicting PPROM prior to symptoms. Using chart review, 18 patients with confirmed cases of PPROM were identified from 2013-2016. Second trimester residual serum was retreived from freezer storage for these cases along with 5 matched controls for each case. The biomarkers biglycan, decorin and SHBG were analyzed first separately, then in combination to determine their ability to predict PPROM. The predictive score for the combined model displays an AUC = 0.774. The ROC curve of the predicted score has an optimal threshold of 0.238 and a sensitivity and specificity of 0.72 and 0.84 respectively. This prenatal serum panel is a promising serum screening-based biochemical model to predict PPROM in asymptomatic women.
Topics: Adolescent; Adult; Biglycan; Biomarkers; Case-Control Studies; Decorin; Female; Fetal Membranes, Premature Rupture; Humans; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Second; Retrospective Studies; Young Adult
PubMed: 32436194
DOI: 10.1007/s43032-020-00192-9 -
Cell Cycle (Georgetown, Tex.) Jun 2012Inflammation is not only a defensive mechanism against microbial invasion, but also frequently represents a critical response to tissue injury under sterile conditions.... (Review)
Review
Inflammation is not only a defensive mechanism against microbial invasion, but also frequently represents a critical response to tissue injury under sterile conditions. It is now well established that tissue injury leads to the release of endogenous molecules of intra- and extracellular origin acting as damage-associated molecular patterns (DAMPs). The small leucine-rich proteoglycans (SLRPs) can act as powerful DAMPs following their proteolytical release from the extracellular matrix. Recent investigations of SLRP signaling networks revealed new levels of complexity, showing that SLRPs can cluster different types of receptors and orchestrate a host of downstream signaling events. This review will summarize the evidence for the multifunctional proinflammatory signaling properties of the two archetypal SLRPs, biglycan and decorin. These secreted proteoglycans link the innate to the adaptive immune response and operate in a broad biological context, encompassing microbial defense, tumor growth and autoimmunity.
Topics: Biglycan; Decorin; Humans; Immunity, Innate; Inflammation; MicroRNAs; Proteoglycans; Receptors, Purinergic; Signal Transduction; Toll-Like Receptors
PubMed: 22580469
DOI: 10.4161/cc.20316 -
Matrix Biology : Journal of the... 2016The small proteoglycan biglycan (Bgn) is highly expressed in the organic matrix of bone and plays a role in bone formation. Previous work implicated Bgn in vessel growth... (Review)
Review
The small proteoglycan biglycan (Bgn) is highly expressed in the organic matrix of bone and plays a role in bone formation. Previous work implicated Bgn in vessel growth during bone healing [1]. By infusing barium sulfate (BaSO4) into WT and Bgn-deficient mice we discovered the positive effect of Bgn in modulating angiogenesis during fracture healing. Using micro-computed tomography angiography we found significant differences in the vessel size and volume among other parameters. To further understand the mechanistic basis for this, we explored the relationship between Bgn and the anti-angiogenic protein endostatin. Immunohistochemistry (IHC) showed co-localization of Bgn and endostatin in regions of bone formation, with increased endostatin staining in Bgn-KO compared to WT at 14days post-fracture. To further elucidate the relationship between Bgn and endostatin, an endothelial cell tube formation assay was used. This study showed that endothelial cells treated with endostatin had significantly decreased vessel length and vessel branches compared to untreated cells, while cells treated with endostatin and Bgn at a 1:1M ratio had vessel length and vessel branches comparable to untreated cells. This indicated that Bgn was able to mitigate the inhibitory effect of endostatin on endothelial cell growth. In summary, these results suggest that Bgn is needed for proper blood vessel formation during fracture healing, and one mechanism by which Bgn impacts angiogenesis is through inhibition of endostatin.
Topics: Animals; Biglycan; Computed Tomography Angiography; Down-Regulation; Endostatins; Endothelial Cells; Fracture Healing; Gene Knockout Techniques; Mice; Neovascularization, Physiologic; X-Ray Microtomography
PubMed: 27072616
DOI: 10.1016/j.matbio.2016.03.008